ZYG-9ch-TOG promotes the stability of acentrosomal poles via regulation of spindle microtubules in C. elegans oocyte meiosis.

During mitosis, centrosomes serve as microtubule organizing centers that guide the formation of a bipolar spindle. However, oocytes of many species lack centrosomes; how meiotic spindles establish and maintain these acentrosomal poles remains poorly understood. Here, we show that the microtubule polymerase ZYG-9ch-TOG is required to maintain acentrosomal pole integrity in C.

Longitudinal Shifts of Solid Tumor and Liquid Biopsy Sequencing Concordance in Metastatic Breast Cancer.

Unlabelled: Tissue-based next-generation sequencing (NGS) in metastatic breast cancer (mBC) is limited by the inability to noninvasively track tumor evolution. Cell-free DNA (cfDNA) NGS has made sequential testing feasible; however, the relationship between cfDNA and tissue-based testing in mBC is not well understood. Here, we evaluate concordance between tissue and cfDNA NGS relative to cfDNA sampling frequency in a large, clinically annotated mBC data set.

Validation of a liquid biopsy assay with molecular and clinical profiling of circulating tumor DNA.

Liquid biopsy is a valuable precision oncology tool that is increasingly used as a non-invasive approach to identify biomarkers, detect resistance mutations, monitor disease burden, and identify early recurrence. The Tempus xF liquid biopsy assay is a 105-gene, hybrid-capture, next-generation sequencing (NGS) assay that detects single-nucleotide variants, insertions/deletions, copy number variants, and chromosomal rearrangements. Here, we present extensive validation studies of the xF assay using reference standards, cell lines, and patient samples that establish high sensitivity, specificity, and accuracy in variant detection.

Hybrid analysis of gene dynamics predicts context-specific expression and offers regulatory insights.

Motivation: To understand the regulatory pathways underlying diseases, studies often investigate the differential gene expression between genetically or chemically differing cell populations. Differential expression analysis identifies global changes in transcription and enables the inference of functional roles of applied perturbations. This approach has transformed the discovery of genetic drivers of disease and possible therapies.

Windowed Granger causal inference strategy improves discovery of gene regulatory networks.

Accurate inference of regulatory networks from experimental data facilitates the rapid characterization and understanding of biological systems. High-throughput technologies can provide a wealth of time-series data to better interrogate the complex regulatory dynamics inherent to organisms, but many network inference strategies do not effectively use temporal information. We address this limitation by introducing Sliding Window Inference for Network Generation (SWING), a generalized framework that incorporates multivariate Granger causality to infer network structure from time-series data.

A systems approach to integrative biology: an overview of statistical methods to elucidate association and architecture.

An organism's ability to maintain a desired physiological response relies extensively on how cellular and molecular signaling networks interpret and react to environmental cues. The capacity to quantitatively predict how networks respond to a changing environment by modifying signaling regulation and phenotypic responses will help inform and predict the impact of a changing global enivronment on organisms and ecosystems. Many computational strategies have been developed to resolve cue-signal-response networks.